Project Summary/Abstract Advances in cancer treatment have resulted in a growing number of cancer survivors in the United States. Despite the success of cancer treatments, survivors face long-term changes in health, with twice the likelihood of disability as those without a cancer history, greater risk for second primary cancers, more age-related comorbid disorders, and 28% reduction in life expectancy. This study hypothesizes that the increased risk of morbidity and mortality in cancer survivors is due to accelerated biological aging. Furthermore given that the risk for the late effects of cancer diagnosis and treatment show considerable variability, individual differences may either confer protection or promote vulnerability. Given our preliminary data that sleep disturbance leads to greater increases in inflammation and telomere erosion over a one year period, we further hypothesize that sleep disturbance and depression history serve as susceptibility factors to accelerate biological aging. To examine these questions, this study leverages an existing project (CA160245) of a Kaiser Permanente Southern California (KPSC) SEER-affiliated tumor registry-based sample of 300 (>55 years) breast cancer survivors, includes biological aging outcomes of cellular and transcriptional markers of inflammation and telomere erosion, and recruits a KPSC comparison cohort of 300 older women without a cancer history. Both KPSC groups will be examined at baseline and prospectively followed at 8, 16, 24, and 32 months to address three specific aims: 1) to examine differences at baseline and in prospective rate of change of cellular and transcriptional markers of inflammation and telomere length as a function of breast cancer survivorship; 2) to examine differences at baseline and in prospective rate of change of cellular and transcriptional markers of inflammation and telomere length as a function of sleep disturbance and breast cancer survivorship; 3) to examine differences at baseline and in prospective rate of change of cellular and transcriptional markers of inflammation and telomere length as a function of depression history and breast cancer survivorship This study will determine whether biological aging is driven by breast cancer status, by independent effects of sleep disturbance or depression history, or by the interaction of these behavioral factors with breast cancer status. Such information is necessary to define the risk population (i.e., breast cancer survivors, depression history) and/or risk factors (i.e., sleep disturbance) in the design, implementation, and delivery of treatments, which selectively target biological aging with greatest efficacy with the potential to reduce risk of age-related morbidities.